Analyzing Device, Sensor Testing Device, Testing Method and Computer-Readable Storage Medium

ABSTRACT

There is provided a sensor testing method including: applying at least one of a first voltage that obtains a response caused by a substance and a second voltage that either obtains no response or substantially no response caused by the substance across a first electrode and a second electrode of a sensor; measuring current flowing between the first electrode and the second electrode; and determining whether or not there is a defect present in the sensor based on a quantity related to an amount of change per specific period of time of a current measured when the first voltage and/or the second voltage have been applied.

CROSS-REFERENCE TO RELATED APPLICATION

This application is based on and claims priority under 35 USC 119 fromJapanese Patent Application No. 2011-021942 filed on Feb. 3, 2011,Japanese Patent Application No. 2011-021943 filed on Feb. 3, 2011, andJapanese Patent Application No. 2011-286060 filed on Dec. 27, 2011, thedisclosures of which are incorporated by reference herein.

BACKGROUND

1. Technical Field

The present invention relates to an analyzing device, a sensor testingdevice, testing method and computer-readable storage medium.

2. Related Art

There is a related proposal for an electro-chemical biosensor in whichplural sets of a working electrode and a counter electrode are provided,and a defect of a sensor is detected by comparing responses between eachelectrode set (see for example specifications of U.S. Pat. No. 7,190,988and U.S. Pat. No. 6,121,009).

There is also a proposal for a method to adjust data collected from asensor in an electro-chemical biosensor (see for example thespecification of U.S. Pat. No. 6,895,263). In the technology of thespecification of U.S. Pat. No. 6,895,263 the correction characteristicsare computed based on a current sensor data point, and a possible erroror a sensitivity change is ascertained from the correctioncharacteristics. In order to determine whether or not the correctioncharacteristics at this time are unpredictable a comparison is madebetween an estimated value related to the correction characteristics andthe correction characteristics at this time, so as to ascertain a faultin the sensor or a change in sensor sensitivity. The estimated valuerelated to the correction characteristics is determined from thecorrection characteristics at that time and from past correctioncharacteristics, and a faulty sensor is determined when at least twounpredictable correction characteristics are received in a row that donot support each other.

There is also a proposal for an electro-chemical sensor monitoringdevice installed with an electro-chemical sensor formed from twoelectrode sets or three electrode sets, in which the current flowingbetween a working electrode and a counter electrode is detected, atransient response time until current reaches a steady state is counted,and the sensor quality is determined with reference to the relationshipbetween the transient response time and correction values (see forexample Japanese Patent Application Laid-Open (JP-A) No. 2004-233294).

However, since a relative comparison is performed between plural sets ofworking electrode and counter electrode provided in the technology ofU.S. Pat. Nos. 7,190,988 and 6,121,009, this technology is not able toascertain whether or not each of the electrode sets is normal inabsolute terms. In particular, since electrode sets in electro-chemicalbiosensors are miniature in size it is conceivable that all of theelectrode sets within a sensor are damaged at the same time, and anissue arises that it is not possible to stably test the sensor state byperforming relative comparison. Furthermore, since plural sets ofelectrodes are required this is also detrimental from the perspectivesof manufacturing and cost.

In the technology of U.S. Pat. No. 6,895,263 there is uncertainty todetermination since a faulty sensor is determined based on an estimatedvalue computed employing sampled data.

In the technology of JP-A No. 2004-233294 there is an issue in that thetime until a steady state is reached may become long.

SUMMARY

In consideration of the above circumstances the present invention isdirected towards an analyzing device capable of stably testing the stateof a sensor in a short time, without providing plural electrode sets,and to a sensor testing device, testing method and computer-readablestorage medium of the same.

An analyzing device according to the first aspect of the presentinvention includes: a sensor section including a reagent layer includinga reagent that reacts with a substance in a sample liquid, an electrodeincluding a first electrode and a second electrode for applying avoltage to the reagent layer, and an external layer membrane for makingcontact with the reagent layer; a voltage application unit for applyingacross the first electrode and the second electrode at least one of afirst voltage that obtains a response caused by the substance and asecond voltage that either obtains no response or substantially noresponse caused by the substance; a current measurement unit formeasuring current flowing between the first electrode and the secondelectrode; and a determination unit for determining whether or not thereis a defect present in the external layer membrane based on at least oneof a first physical quantity related to an amount of change per specificperiod of time of a first current measured by the current measurementunit when the first voltage has been applied and a second physicalquantity related to an amount of change per specific period of time of asecond current measured by the current measurement unit when the secondvoltage has been applied.

According to the above analyzing device, a sensor section has a reagentlayer including a reagent that reacts with a substance in a sampleliquid, an electrode including a first electrode and a second electrodefor applying a voltage to the reagent layer, and an external layermembrane for making contact with the reagent layer. When the voltageapplication unit applies across the first electrode and the secondelectrode at least one of a first voltage that obtains a response causedby the substance and a second voltage that either obtains no response orsubstantially no response caused by the substance, a current measurementunit measures current flowing between the first electrode and the secondelectrode. Then, the determination unit determines whether or not thereis a defect present in the external layer membrane based on at least oneof a first physical quantity related to an amount of change per specificperiod of time of a first current measured by the current measurementunit when the first voltage has been applied and a second physicalquantity related to an amount of change per specific period of time of asecond current measured by the current measurement unit when the secondvoltage has been applied. The first physical quantity and the secondphysical quantity may be amount of change per specific period of time ofthe respective currents themselves, or other physical quantities thatcan be derived therefrom.

Accordingly, by employing the physical quantity related to amount ofchange in the current when at least one of the first voltage thatobtains a response caused by the substance and the second voltage thateither obtains no response or substantially no response caused by thesubstance to test the state of the external layer membrane, the state ofthe sensor can be tested stably and in a short time without providingplural sets of electrodes.

The first physical quantity may be a first time from until the amount ofchange per specific period of time of the first current reaches a valuein a predetermined first specific range and the second physical quantitymay be a second time until the amount of change per specific period oftime of the second current reaches a value in a predetermined secondspecific range. By using such quantities, a defect present in theexternal layer membrane can be detected in shorter time as compared tocases employing the time for current to reach a steady state.

The analyzing device may further include a correction unit that correctsthe current value measured by the current measurement unit when a defectis determined by the determination unit to have occurred in the externallayer membrane, the correction unit performing correction based on atleast one of a predetermined first relationship between the firstphysical quantity and a defect ratio of the external layer membrane anda predetermined second relationship between the second physical quantityand a defect ratio of the external layer membrane. In other words, thefirst physical quantity and the second physical quantity obtained whenthe first voltage and the second voltage are respectively applied changein response to the defect ratio of the external layer membrane.Therefore, the measured current value can be corrected based on thedefect ratio derived from these physical quantities. More specifically,the correction unit may estimate the defect ratio based on at least oneof the first relationship and the second relationship, and correct thecurrent value measured by the current measurement unit based on apredetermined relationship between the defect ratio of the externallayer membrane and the current value measured from the sensor sectionprovided with an external layer membrane having defects corresponding tothe defect ratio.

When the correction unit estimates the defect ratio based on both thefirst relationship and the second relationship, the correction unit maycompute the defect ratio as the average value, the maximum value or theminimum value of a first defect ratio estimated based on the firstrelationship and a second defect ratio estimated based on the secondrelationship.

The analyzing device may further include an output unit that outputs asignal indicating that a defect has occurred in the sensor section whena defect is determined to have occurred in the external layer membraneby the determination unit.

In the analyzing device, when applying both the first voltage and thesecond voltage the voltage application unit may apply the first voltageand the second voltage alternately.

In the analyzing device, the current measurement unit may continuouslymeasure the current flowing between the first electrode and the secondelectrode, and the determination unit may determine the presence orabsence of a defect in the external layer membrane at a predeterminedtiming. Since it is desirable to be able to test the sensor in a shorttime in a device that continuously monitors current in this manner suchas, for example, in a continuous blood sugar monitoring device,application of the analyzing device of the present invention is highlyeffective.

During use of the analyzing device the sensor section may be disposedunder the skin of a user of the analyzing device and the reagent layerreacts to a composition to be tested present under the skin.

Moreover, the reagent layer may extract electrons from the compositionto be tested and may supply the extracted electrons to the electrode.

Furthermore, the reagent layer may include an enzyme portion forextracting electrons from the composition to be tested.

A sensor testing device according to the second aspect of the presentinvention includes: a voltage application unit that applies at least oneof a first voltage that obtains a response caused by a substance and asecond voltage that either obtains no response or substantially noresponse caused by the substance across a first electrode and a secondelectrode of a sensor section configured with a reagent layer includinga reagent that reacts with the substance in a sample liquid, anelectrode including the first electrode and the second electrode forapplying a voltage to the reagent layer, and an external layer membranefor making contact with the reagent layer; a current measurement unitthat measures current flowing between the first electrode and the secondelectrode; and a determination unit that determines whether or not thereis a defect present in the external layer membrane based on at least oneof a first physical quantity related to an amount of change per specificperiod of time of a first current measured by the current measurementunit when the first voltage has been applied and a second physicalquantity related to an amount of change per specific period of time of asecond current measured by the current measurement unit when the secondvoltage has been applied. For instance, the present device can beemployed to test the state of the external layer membrane of sensors ina sensor manufacturing process, such as in a factory where sensors arebeing manufactured.

A sensor testing method according to the third aspect of the presentinvention includes: applying at least one of a first voltage thatobtains a response caused by a substance and a second voltage thateither obtains no response or substantially no response caused by thesubstance across a first electrode and a second electrode of a sensorsection configured with a reagent layer including a reagent that reactswith the substance in a sample liquid, an electrode including the firstelectrode and the second electrode for applying a voltage to the reagentlayer, and an external layer membrane for making contact with thereagent layer; measuring current flowing between the first electrode andthe second electrode; and determining whether or not there is a defectpresent in the external layer membrane based on at least one of a firstphysical quantity related to an amount of change per specific period oftime of a first current measured when the first voltage has been appliedand a second physical quantity related to an amount of change perspecific period of time of a second current measured when the secondvoltage has been applied.

The fourth aspect of the present invention is a computer-readablestorage medium storing a program for causing a computer to execute asensor testing method, the sensor testing method including: by a voltageapplication unit, applying at least one of a first voltage that obtainsa response caused by a substance and a second voltage that eitherobtains no response or substantially no response caused by the substanceacross a first electrode and a second electrode of a sensor sectionconfigured with a reagent layer including a reagent that reacts with thesubstance in a sample liquid, an electrode including the first electrodeand the second electrode for applying a voltage to the reagent layer,and an external layer membrane for making contact with the reagentlayer; by a current measurement unit, measuring current flowing betweenthe first electrode and the second electrode; and by a determinationunit, determining whether or not there is a defect present in theexternal layer membrane based on at least one of a first physicalquantity related to an amount of change per specific period of time of afirst current measured by the current measurement unit when the firstvoltage has been applied and a second physical quantity related to anamount of change per specific period of time of a second currentmeasured by the current measurement unit when the second voltage hasbeen applied.

Accordingly, by employing the physical quantity related to amount ofchange in the current when at least one of the first voltage thatobtains a response caused by the substance and the second voltage thateither obtains no response or substantially no response caused by thesubstance to test the state of the external layer membrane, the state ofthe sensor can be tested stably and in a short time without providingplural sets of electrodes.

BRIEF DESCRIPTION OF THE DRAWINGS

Exemplary embodiments of the present invention will be described indetail based on the following figures, wherein:

FIG. 1 is a cross-section illustrating a continuous glucose monitoringdevice of an exemplary embodiment;

FIG. 2 is a perspective view of a sensor section with an enlargeddiagram of a portion thereof;

FIG. 3 is a cross-section illustrating an end portion (electrodeportion) of a sensor section;

FIG. 4 is a block diagram illustrating a schematic configuration of acircuit board;

FIG. 5 is a graph illustrating response current when a response voltagehas been applied;

FIG. 6 shows images of states of CA membranes of a sensor section;

FIG. 7 is a graph illustrating changes in response current afterapplication of a response voltage.

FIG. 8 is a graph illustrating the time until the amount of change ofthe response current becomes less than a change amount threshold valuefor each sensor with a different CA membrane state when a responsevoltage has been applied;

FIG. 9 is a flow chart illustrating a testing mode processing routineexecuted in a continuous glucose monitoring device of a first exemplaryembodiment;

FIG. 10 is a graph illustrating a relationship between the time untilthe amount of change of the response current becomes less than a changeamount threshold value with respect to a defect ratio when a responsevoltage has been applied;

FIG. 11A and FIG. 11B are graphs illustrating relationships between adefect ratio with respect to a sensitivity normal-error difference;

FIG. 12 is a graph illustrating the amount of change of the responsecurrent for each sensor with a different CA membrane state, when aresponse voltage has been applied;

FIG. 13 is a flow chart illustrating a testing mode processing routineexecuted in a continuous glucose monitoring device of a second exemplaryembodiment;

FIG. 14 is a graph illustrating a relationship between the amount ofchange of the response current with respect to a defect ratio when aresponse voltage has been applied;

FIG. 15A is a graph illustrating changes in response current afterapplication of a response voltage and FIG. 15B is a graph illustratingchanges in response current after application of a non-response voltage;

FIG. 16A and FIG. 16B are graphs illustrating the time until the amountof change of the response current becomes less than a change amountthreshold value for each sensor with a different CA membrane state whena response voltage has been applied, with FIG. 16A illustrating when aresponse voltage has been applied and FIG. 16B illustrating when anon-response voltage has been applied;

FIG. 17 is a flow chart illustrating a testing mode processing routineexecuted in a continuous glucose monitoring device of a third exemplaryembodiment;

FIG. 18A and FIG. 18B are graphs illustrating a relationship between thetime until the amount of change of the response current becomes lessthan a change amount threshold value with respect to a defect ratio,with FIG. 18A illustrating when a response voltage has been applied andFIG. 18B illustrating when a non-response voltage has been applied;

FIG. 19 is a graph illustrating the amount of change of the responsecurrent for each sensor with a different CA membrane state, when anon-response voltage has been applied;

FIG. 20 is a graph illustrating a relationship between the amount ofchange of the response current with respect to a defect ratio when anon-response voltage has been applied;

FIG. 21 shows diagrams illustrating other examples of voltage patterns;and

FIG. 22A and FIG. 22B show cross-sections illustrating other examples ofend portions (electrode portions) of a sensor section;

DETAILED DESCRIPTION

Explanation follows regarding an exemplary embodiment of the presentinvention, with respect to the drawings. In the present exemplaryembodiment explanation is given of a case in which the analyzing deviceof the present invention is applied to a Continuous Glucose Monitoring(CGM) device.

First Exemplary Embodiment

As shown in FIG. 1, a continuous glucose monitoring device 1 of thepresent exemplary embodiment is configured including a housing 2, acircuit board 3, and a sensor section 4. The continuous glucosemonitoring device 1 is applied to skin 6 such as an abdominal orshoulder region of a human body, and continuously monitors theconcentration of glucose in the blood or in interstitial subcutaneousfluid.

The housing 2 is configured with a cover 20 and a base 21 forming theexternal profile of the continuous glucose monitoring device 1. Thecover 20 and the base 21 are joined together so as to house the circuitboard 3 in the space formed between the cover 20 and the base 21. Amaterial with extremely low moisture transmissivity, for example a metalor a polypropylene resin, is preferably employed for the housing 2.

The base 21 is formed with an insertion hole for inserting the sensorsection 4, and an end portion 40 of the sensor section 4 is fixed at theinside face of the base 21. A bonding film 5 is provided on the outsideface of the base 21. An adhesive tape is employed on both faces of thebonding film 5. The bonding film 5 is itself attached to the base 21through the tape on one face, and the continuous glucose monitoringdevice 1 is attached to the skin 6 through the tape on the other face.

The circuit board 3 is equipped with electronic configuration elementsrequired for overall control of the continuous glucose monitoring device1. The circuit board 3 is configured including a connection portion 30for making contact with an electrode 42 (see FIG. 2) of the sensorsection 4, described later. The connection portion 30 is employed toapply a voltage to the sensor section 4 and obtain a response current.

The sensor section 4 obtains a response that depends on the glucoseconcentration in the blood or interstitial subcutaneous fluid. A firstend portion 40 of the sensor section 4 makes contact with the connectionportion 30 of the circuit board 3, and the second end portion of thesensor section 4 is inserted into the skin 6.

As shown in FIG. 2, the sensor section 4 is configured including a base41, the electrode 42 and an enzyme portion 43.

The base 41 is configured in sheet form from a flexible, electricallyinsulating material and supports the electrode 42. An end portion 41B ofthe base 41 on the side for insertion into the skin 6 is formed with asharp profile, enabling the sensor section 4 to be easily inserted intothe skin 6 and enabling pain of a user to be reduced. However, there areno particular limitations to the profile of the leading end of the base41, and configuration may be made with a profile other than a sharpenedprofile. A material that has appropriate electrical insulatingproperties so as not to affect the human body can be employed as thematerial for the base 41, and, for example, a thermoplastic resin suchas polyethylene terephthalate (PET), polypropylene (PP) or polyethylene(PE) may be employed therefor. A thermoset resin such as a polyimideresin or an epoxy resin may also be employed therefor.

The electrode 42 is configured including a working electrode portion 42Aand a counter electrode portion 42B. By applying a voltage to theelectrode 42 a current flows between the working electrode portion 42Aand the counter electrode portion 42B corresponding to electronsextracted by the enzyme portion 43, described later.

The enzyme portion 43 acts to extract electrons from the glucose andpass the extracted electrons across to the working electrode portion42A. The enzyme portion 43 can, for example, be a glucose oxidoreductasedisposed on the working electrode portion 42A. A glucose oxidase (GOD)or a glucose dehydrogenase (GDH) can be employed as the glucoseoxidoreductase. A known method can be employed as the method foraffixing the glucose oxidoreductase, such as for example employing amethod that uses a polymerizable gel, polyacrylamide, or a polymer suchas phosphorus, a method that uses a MPC polymer of a phospholipidpolymer coupled using a silane coupling agent, or a method using proteincoating.

FIG. 3 schematically illustrates a cross-section configuration of theend portion 41B of the sensor section 4. The working electrode portion42A and the counter electrode portion 42B are formed on the base 41, anda semi-permeable membrane 45 is formed so as to cover the workingelectrode portion 42A. The region configured by the base 41 and thesemi-permeable membrane 45 is a reagent layer 44 and the enzyme portion43 is disposed within the reagent layer 44. The enzyme portion 43 neednot necessarily be affixed on the working electrode portion 42A, andconfiguration may be made such that the enzyme portion 43 is disposedwithin the reagent layer 44, above the working electrode portion 42A butnot making contact with the working electrode portion 42A.

The semi-permeable membrane 45 is provided to prevent sensor sensitivityfrom becoming saturated immediately, for example to prevent sensitivitysaturation to an upper limit of detectable concentration of glucose forthe sensor, and the semi-permeable membrane 45 restricts passage ofglucose to the enzyme portion 43. The semi-permeable membrane 45 alsosuppresses the passing through to the enzyme portion 43 of interferingsubstances that would impede reaction. A cellulose acetate membrane orpolyurethane membrane may be employed as the semi-permeable membrane 45.In the present exemplary embodiment a case will be explained in which acellulose acetate membrane is employed as the semi-permeable membrane 45(referred to below as CA membrane). Note that the semi-permeablemembrane 45 is one example of an external membrane in the presentinvention. However, the external membrane is not limited to materialshaving a property of restricting passage of glucose to the enzymeportion 43.

The method of forming the sensor section 4 is by, for example, formingthe working electrode portion 42A and the counter electrode portion 42Bon the base 41 by screen printing employing a carbon ink, covalentbonding a carbodiimide thereon, dripping a bridged glucoseoxidoreductase thereon using glutaraldehyde (GA) as the bridging agent,and then drying with warm air at 40° C. for 15 minutes. Then a CAmembrane can be formed as the semi-permeable membrane 45 using spincoating or dip coating so as to form a covering. Configuration may alsobe made with such compounds as a bis (sulphosuccinimidyl) suberate orbis-N-succinimidyl-(nonaethylene glycol) ester.

As shown in FIG. 4, the circuit board 3 is configured including theconnection portion 30 and also a communication unit 31, a power supply32, a control unit 33, a computation unit 34 and a storage unit 35.

The communication unit 31 performs data communication between thecontinuous glucose monitoring device 1 and an external data processingapparatus. The communication unit 31 is configured including at least atransmission unit, and as required also includes a reception unit. Datacommunication may be by means of, for example, wireless communicationsuch as infrared communication or Bluetooth. Configuration may also bemade such that wired data communication is performed, and in such casesa cable connecting portion is provided to the communication unit 31 ofthe continuous glucose monitoring device 1, such that data communicationis performed by connecting with a cable to an external data processingapparatus, for example.

Examples of an external data processing apparatus include such anapparatus as an insulin supply device for administering insulin to ahuman body, a simple blood sugar measurement instrument, a wrist watchsize display device, and a personal computer (PC).

In data communication between the continuous glucose monitoring device 1and a simple blood sugar measurement instrument, for example, a bloodsugar measurement result of the simple blood sugar measurementinstrument can be transmitted to the continuous glucose monitoringdevice 1. The measurement result of the continuous glucose monitoringdevice 1 and the blood sugar measurement result received from the simpleblood sugar measurement instrument can accordingly be compared, enablingcorrection of the measurement results of the continuous glucosemonitoring device 1 to be performed. Configuration may be made such thatthe data (current values) measured by the continuous glucose monitoringdevice 1 are transmitted to the simple blood sugar measurementinstrument such that the blood sugar values themselves are computed inthe simple blood sugar measurement instrument.

In data communication between the continuous glucose monitoring device 1and a wrist watch size display device, for example, the measurementresult of the continuous glucose monitoring device 1 can be transmittedto the wrist watch size display device. Such an approach enables a userto easily ascertain the measurement results even when the continuousglucose monitoring device 1 is mounted to a location that is difficultfor a user to see, such as a user's shoulder or abdominal region.

Data communication between the continuous glucose monitoring device 1and a PC, for example, enables the data (current values) measured by thecontinuous glucose monitoring device 1 to be transmitted to the PC. Theglucose concentration trend can be displayed and various analyses canthen be performed by the PC. Configuration may be made such thatcorrection data or the like is transmitted from a PC to the continuousglucose monitoring device 1.

The power supply 32 is a direct current power source for supplying powerto the circuit board 3 and the sensor section 4, and a battery with a 1to 3V power supply voltage can be employed, for example.

The control unit 33 controls the continuous glucose monitoring device 1overall, controlling, for example, such aspects as the voltageapplication timing, response current sampling, glucose concentrationcomputation processing and communication to an external data processingapparatus.

The computation unit 34 executes various computations required inprocessing in the continuous glucose monitoring device 1, including forexample computation of the glucose concentration.

Programs, such as a program for executing a testing mode processingroutine, described later, various programs for execution by the controlunit 33, and data such as a correction curve, correction data andvoltage application patterns employed in computations of the computationunit 34 are stored in the storage unit 35. The response current detectedby the sensor section 4 and the glucose concentration data computed bythe computation unit 34 are also stored in the storage unit 35.

The control unit 33, the computation unit 34 and the storage unit 35 maybe configured by electrical components such as a CPU and/or an MPU, ROMand RAM mounted on the circuit board 3.

In the thus configured continuous glucose monitoring device 1 of thepresent exemplary embodiment, in a monitoring mode the response currentis measured when a predetermined voltage pattern, such as illustrated inFIG. 5, is applied. In the testing mode the state of the sensor section4, and in particular the state of the semi-permeable membrane 45, istested based on changes in response current when a voltage that obtainsa response caused by glucose is applied.

Explanation follows regarding the principles of the testing mode in thecontinuous glucose monitoring device 1 of the first exemplaryembodiment.

For example, the voltage pattern illustrated in FIG. 5 is a pattern inwhich a voltage that does not obtain a response caused by glucose(referred to below as non-response voltage E1) is applied for a specificperiod of time (−200 mV for 240 seconds in this example), followed byapplication of a voltage that obtains a response caused by glucose(referred to below as response voltage E2) for a specific period of time(400 mV for 120 seconds in this example). The testing mode in the firstexemplary embodiment utilizes the amount of change in response currentfrom immediately after application of the response voltage E2.

The non-response voltage E1 is a voltage to which glucose does notrespond at all or a voltage to which glucose exhibits a slight response,but at a level which in practice can be considered as no response. Moreprecisely, the response current when the non-response voltage E1 isapplied to the sensor section 4 includes extremely small responsescaused by glucose, but is mainly caused by external environmentalbackground factors such as background due to the particularities of thesensor, and background and noise of co-present substances. The magnitudeof the non-response voltage E1 is set based on the specification of thesensor section 4 (for example according to factors such as the amount ofenzyme used, the method of affixing the enzyme, the material of theelectrodes and the response region). More specifically, the non-responsevoltage E1 is set in a range of −0.5V to +0.5V (preferably −25 mV to +25mV) from the response initiation voltage at which the response currentcaused by glucose starts to flow when the voltage applied to the sensorsection 4 is increased.

The response voltage E2 is a voltage at which glucose exhibitssufficient response. The magnitude of the response voltage E2 is setbased on the specification of the sensor section 4 (for example factorssuch as the amount of enzyme used, the method of affixing the enzyme,the material of the electrodes and the response region).

FIG. 5 illustrates response currents when such a voltage pattern isapplied to plural sensors with different states of semi-permeablemembrane 45 (CA membrane). The glucose concentration is 100 mg/dL. Thestates of the CA membranes of each of the respective plural sensors are,as shown in FIG. 6, (1) no CA membrane (NoCA), (2) with CA membrane(YesCA), and (3) through (6) simulated defective membranes with 4%concentration CA membrane only covering a portion of the sensor section4 (CA4% Spin-A to -D). For FIG. 6 (3) through (6), the dark portions atthe lower part of the figure are the parts covered by the CA membrane.The defect ratio for each sensor (a proportion of an area that is notcovered by the CA membrane with respect to the area of the sensorsection) is, respectively, (1) 100 percent, (2) 0 percent, (3) 65percent, (4) 64 percent, (5) 35 percent, and (6) 10 percent. Moreover,for (2) with CA membrane (YesCA), CA membrane examples concentrations of2% (CA2% Spin), 3% (CA3% Spin) and 4% (CA4% Spin) are prepared. Due tothe difficulties in actually measuring the membrane thickness of the CAmembrane the membrane thickness of the CA membranes are indicated byconcentrations of the membranes.

The amount of change in the response current from immediately afterapplication of the response voltage E2 (+400 mV) for each of the sensorsis illustrated in FIG. 7. The sampling interval employed is 5 seconds. Agraph illustrating the time until the absolute values of the amount ofchange in response current every 5 seconds ΔnA/mm²/5 s becomes smallerthan specific change amount threshold values (here, set at 0.2 nA/mm²)are shown in FIG. 8. As seen from these graphs, the period of time untilthe change in response current becomes small is earlier for thinnermembrane thickness sensors CA3% Spin and CA2% Spin than for the thickestsensor CA4% Spin. The cause of this difference in time is postulated tobe due to response delay based on the glucose permeability restrictionby the CA membrane. Moreover, the time until the change of the responsecurrent becomes smaller is earlier in the sensors with simulateddefective membranes CA4% Spin-A to -D than in the CA4% Spin sensor withcompletely covered surface.

Taking a normal state as a CA4% Spin sensor, by utilizing these resultsit is possible to ascertain a state in which the membrane thickness ofthe CA membrane has become thinned, and a state in which a portion ofthe CA membrane has been damaged, at the manufacturing stage or duringuse. In this case the change amount threshold value is 0.2 nA/mm²,however the change amount threshold values are appropriately setaccording to such factors as the specification of the sensor section 4and the sampling periods.

Explanation follows regarding a testing mode processing routine executedduring the testing mode of the continuous glucose monitoring device 1 ofthe first exemplary embodiment, with reference to FIG. 9.

At step 100 determination is made as to whether or not it is a timingfor executing the processing of the testing mode. For exampleconfiguration may be determined such that the testing mode is executedevery hour, or executed at predetermined times, and determination atthis step is whether or not such a time has arrived. Configuration mayalso be made such that the execution timing of the testing mode isdetermined to be in the night time when there will be little influenceon continuous monitoring. Configuration may also be made such thatimmediately after starting to use the continuous glucose monitoringdevice 1 the timing of testing mode execution is determined, for exampleso as to be executed on the seventh day from start of use, when no rapidchange in the state of the sensor is anticipated. Processing transitionsto step 102 when determined that the execution timing for the testingmode has arrived. However when determined that the execution timing forthe testing mode has not yet arrived determination at step 100 isrepeated until determined that the execution timing has arrived.

In step 102 the response voltage E2 is applied. For example a voltage of+400 mV is applied for 120 seconds. Then, in step 104, at a specificsampling interval (for example 5 seconds), the amount of change of theresponse current ΔI is measured. Then at step 106, with the timing atwhich the response voltage E2 is applied at step 102 as a startingpoint, the time T until the measured amount of change of the responsecurrent ΔI becomes smaller than a specific change amount threshold valueΔIth in the specific period of time when the response voltage E2 isapplied is computed. Note that explanation is made of a case in whichthe amount of change of the response current ΔI is an absolute value.However, it is not limited to an absolute value, and the actual valuemay be employed. In such a case, the time T until the amount of changeof the response current ΔI becomes larger than a specific change amountthreshold value ΔIth is computed. In other words, the time T until theamount of change of the response current ΔI reaches a value in aspecific range can be computed.

Then at step 108, comparison is made of the time T computed at step 106and a time threshold value Tth and determination is made as to whetheror not the time T is smaller than the time threshold value Tth. The timethreshold value Tth is set with reference to the time when the responsevoltage E2 is applied until the amount of change of the response currentAI becomes smaller than the change amount threshold value ΔIth for acase when a sensor with normal semi-permeable membrane 45 is employed.For example, as shown in FIG. 8, with CA4% Spin as a normal sensor, thetime threshold value Tth can be set at 70±α seconds where a can bebetween 5 to 20 seconds. When time T<time threshold value Tth,determination is made that the state of the semi-permeable membrane 45has changed, namely that a defect has occurred, and processingtransitions to step 110. However, when time T≧time threshold value Tth,determination is made that the state of the semi-permeable membrane 45has not changed, that is, the semi-permeable membrane 45 is in a normalstate, and the processing is ended.

At step 110, the defect ratio of the semi-permeable membrane 45 isderived based on the time T computed at step 106. Then, a correctionvalue for the response current to be measured in the monitoring modecorrected according to the defect ratio is computed and stored in thestorage unit 35.

More specifically, first the relationship between the time T and thedefect ratio is plotted, as shown in FIG. 10. For instance, for each ofthe sensors shown in FIG. 6, the times T in the case the change amountthreshold value ΔIth is set at 0.2 nA/mm² are computed, and therelationship between the times T and the defect ratios for each of thesensors are plotted on a graph with the horizontal axis as time T andthe vertical axis as the defect ratio. Moreover, the defect ratio may betaken as the proportion the membrane thickness (concentration) of the CAmembrane of the sensor is smaller with respect to the membrane thickness(concentration) of the CA membrane of a normal sensor. A correspondencebetween the plotted time T and the defect ratio is derived andpre-stored in the storage unit 35. The correspondence of the time T tothe defect ratio is then employed to derive the defect ratiocorresponding to a time T computed at step 106. For example, in theexample of FIG. 10, if the time T is 60 seconds then the defect ratio isderived as 31.5%.

Here, FIG. 11A shows the relationship between the response currentsensitivity obtained 100 seconds after applying the response voltage E2with respect to the defect ratios of the CA membranes (1) through (6)shown in FIG. 6. Note that obtaining the response current sensitivity isnot limited to this timing and the response current sensitivity can beobtained at any timing within the range in which there is a discernableamount of response current sensitivity. Then, for example as shown inFIG. 11B, the relationship between the defect ratio and a sensitivitynormal-error difference of the sensor is plotted. The sensitivitynormal-error difference is indicated as a proportion with normalresponse sensitivity taken as 100. Depending on the defect ratio thereis a % increase compared to a normal sensor for the point at whichdetermination can be made of whether or not response current is output.The correspondence between the plotted defect ratio and the sensitivitynormal-error difference is derived and pre-stored in the storage unit35. Then the correspondence between the defect ratio and the sensitivitynormal-error difference is employed to derive the sensitivitynormal-error difference corresponding to the derived defect ratio. Forexample in the example of FIG. 11, when the defect ratio is 31.5% asensitivity normal-error difference of about 185.2% is derived. Thissensitivity normal-error difference is then stored in the storage unit35 and processing ended.

In the monitoring mode the response current values actually measured arecorrected, for example to a measured value/correction value using theabove correction value, with this then output as the measurement result.

As explained above, according to the continuous glucose monitoringdevice of the first exemplary embodiment, the time employed to test thestate of the semi-permeable membrane is the time until the amount ofchange of the response current immediately after a voltage that obtainsa response caused by glucose is applied becomes less than apredetermined change amount threshold value. Hence sensor state testingcan be performed stably and in a short time without providing pluralsets of working electrodes and counter electrodes. In particular, sincethe change in response current immediately after voltage application isemployed for testing, the execution time for the testing mode can bemade shorter than in cases employing the time until the response currentreaches a steady state. This is more efficient in cases such as thepresent exemplary embodiment in which continuous monitoring isperformed. In the first exemplary embodiment, explanation is given of acase in which a defect in a sensor is determined based on the time Tuntil the amount of change of the response current ΔI when the responsevoltage E2 is applied (the first voltage) becomes smaller than a changeamount threshold value ΔIth. However, configuration may be made in whichthe time T until the amount of change of the response current ΔI when anon-response voltage E1 is applied reaches a value within a specificrange is used.

Second Exemplary Embodiment

Next, the second exemplary embodiment is explained. The second exemplaryembodiment differs from the first exemplary embodiment in that thedefect ratio of the sensor is determined based on the amount of changeof the response current ΔI itself after the response voltage E2 isapplied. Note that the configuration of the continuous glucosemonitoring device 1 of the second exemplary embodiment is the same asthe continuous glucose monitoring device 1 of the first exemplaryembodiment. Hence, the explanation thereof is omitted.

Hereafter, explanation will be made of the principles of the testingmode in the continuous glucose monitoring device 1 of the secondexemplary embodiment.

As in the first exemplary embodiment, the amount of change in theresponse current a predetermined period (here, 40 seconds) afterapplication of the response voltage E2 (+400 mV) using each of thesensors shown in FIG. 6 is illustrated in FIG. 12. As seen from FIG. 12,the change in response current is larger for thinner membrane thicknesssensors CA3% Spin and CA2% Spin than for the thickest sensor CA4% Spin.The cause of this is postulated to be due to response delay based on theglucose permeability restriction by the CA membrane. Moreover, thechange of the response current is larger in the sensors with simulateddefective membranes CA4% Spin-A to -D than in the CA4% Spin sensor withcompletely covered surface.

Taking a normal state as a CA4% Spin sensor, by utilizing these resultsit is possible to ascertain, a state in which the membrane thickness ofthe CA membrane has become thinned and a state in which a portion of theCA membrane has been damaged, at the manufacturing stage or during use.

Explanation follows regarding a testing mode processing routine executedduring the testing mode of the continuous glucose monitoring device 1 ofthe second exemplary embodiment, with reference to FIG. 13. Note thatthe same processing in the testing mode processing routine of the firstexemplary embodiments is given the same reference numeral and theexplanation thereof is omitted.

At step 100 determination is made as to whether or not it is a timingfor executing the processing of the testing mode. Processing transitionsto step 102 when determined that the execution timing for the testingmode has arrived. However, when determined that the execution timing forthe testing mode has not yet arrived, determination at step 100 isrepeated until determined that the execution timing has arrived.

In step 102 the response voltage E2 is applied for a specific length oftime. For example a voltage of +400 mV is applied for 40 seconds. Thenat step 204, with the timing at which the response voltage E2 is appliedin step 102 as a starting point, the amount of change of the responsecurrent ΔI is measured at a specific time thereafter.

Then at step 208, determination is made as to whether or not the amountof change of the response current ΔI measured in step 204 is larger thana specific change amount threshold value. When it is determined thatΔI>change amount threshold value ΔIth, the state of the semi-permeablemembrane 45 is determined to have changed, namely that a defect hasoccurred, and processing transitions to step 210. However, when it isdetermined that AI change amount threshold value ΔIth, the state of thesemi-permeable membrane 45 is determined not to have changed, that is,the semi-permeable membrane 45 is in a normal state, and the processingis ended. Note that explanation is made of a case in which the amount ofchange of the response current ΔI is an actual value. However, it is notlimited to this, and an absolute value may be employed. In such a case,determination is made as to whether or not the amount of change of theresponse current ΔI becomes smaller than a specific change amountthreshold value ΔIth.

At step 210, the defect ratio of the semi-permeable membrane 45 isderived based on the amount of change of the response current ΔIcomputed at step 204. Then, a correction value for the response currentto be measured in the monitoring mode corrected according to the defectratio is computed and stored in the storage unit 35.

More specifically, first the relationship between the amount of changeof the response current ΔI and the defect ratio is plotted, as shown inFIG. 14. For instance, for each of the sensors shown in FIG. 6, thechange amount threshold value AIM is set at −0.2 nA/mm², and therelationship between the amount of change of the response current ΔI andthe defect ratio for each sensor is plotted on a graph with thehorizontal axis as representing the amount of change of the responsecurrent ΔI and the vertical axis as representing the defect ratio. Acorrespondence between the amount of change of the response current ΔIand the defect ratio is derived and pre-stored in the storage unit 35.The correspondence of the amount of change of the response current ΔI tothe defect ratio is then employed to derive the defect ratiocorresponding to the amount of change of the response current ΔImeasured at step 204. Then, as in the first exemplary embodiment, thederived relationship between the defect ratio and the sensitivitynormal-error difference is employed to derive the sensitivitynormal-error difference corresponding to the derived defect ratio.

As explained above, according to the continuous glucose monitoringdevice of the second exemplary embodiment, the amount of change of theresponse current at a specific time after an immediate application of avoltage that obtains a response caused by glucose is used to test thestate of the semi-permeable membrane. Hence sensor state testing can beperformed stably and in a short time without providing plural sets ofworking electrodes and counter electrodes. In particular, since thechange in response current immediately after voltage application isemployed for testing, the execution time for the testing mode can bemade shorter than in cases employing the time until the response currentreaches a steady state. This is more efficient in cases such as thepresent exemplary embodiment in which continuous monitoring isperformed.

In the second exemplary embodiment, explanation is given of a case inwhich a defect in a sensor is determined based on the amount of changeof the response current AI when the response voltage E2 is applied (thefirst voltage). However, configuration may be made in which the amountof change of the response current ΔI when a non-response voltage E1 isapplied is used.

Third Exemplary Embodiment

Next, the third exemplary embodiment is explained. The third exemplaryembodiment differs from the first exemplary embodiment in that thedefect ratio of the sensor is determined based on both of the times Tafter the response voltage E2 and the non-response voltage E1 areapplied. Note that the configuration of the continuous glucosemonitoring device 1 of the third exemplary embodiment is the same as thecontinuous glucose monitoring device 1 of the first exemplaryembodiment. Hence, the explanation thereof is omitted.

In the continuous glucose monitoring device 1 of the third exemplaryembodiment, in a monitoring mode the response current is measured when apredetermined voltage pattern, such as illustrated in FIG. 5, isapplied. In the testing mode the state of the sensor section 4, and inparticular the state of the semi-permeable membrane 45, is tested basedon changes in response current when a voltage that obtains a responsecaused by glucose is applied, and on changes to the response currentwhen a voltage that does not obtain a response caused by glucose isapplied.

Explanation follows regarding the principles of the testing mode in thecontinuous glucose monitoring device 1 of the third exemplaryembodiment.

As in the first exemplary embodiment, the amount of change in theresponse current from immediately after application of the responsevoltage E2 (+400 mV) for each of the sensors shown in FIG. 6 isillustrated in FIG. 15A. The amount of change in the response current ofthe non-response voltage E1 (−200 mV) for each of the sensors isillustrated in FIG. 15B. Note that FIG. 15A is the same as FIG. 7. Thesampling interval employed is 5 seconds. Graphs illustrating the timeuntil the absolute values of the amount of change in response currentevery 5 seconds ΔnA/mm²/5 s becomes smaller than specific change amountthreshold values are shown in FIG. 16A and FIG. 16B. FIG. 16Aillustrates when the response voltage E2 is applied, and FIG. 16Billustrates when the non-response voltage E1 is applied. Note that FIG.16A is the same as FIG. 8. The change amount threshold value when theresponse voltage E2 is applied is set at 0.2 nA/mm² and the changeamount threshold value when the non-response voltage E1 is applied isset at 0.5 nA/mm² As seen from these graphs, the period of time untilthe change in response current becomes small is earlier for thinnermembrane thickness sensors CA3% Spin and CA2% Spin than for the thickestsensor CA4% Spin. The cause of this difference in time when the responsevoltage E2 is applied is postulated to be due to response delay based onthe glucose permeability restriction by the CA membrane. The cause ofthis difference in time when the non-response voltage E1 is applied ispostulated to be due to the difference in charge amount of the electricdouble layer on the electrode arising from the difference in states ofthe CA membrane. The time until the change of the response currentbecomes smaller is earlier in the sensors with simulated defectivemembranes CA4% Spin-A to -D than in the CA4% Spin sensor with completelycovered surface.

Taking a normal state as a CA4% Spin sensor, by utilizing these resultsit is possible to ascertain a state in which the membrane thickness ofthe CA membrane has become thinned, and a state in which a portion ofthe CA membrane has been damaged, at the manufacturing stage or duringuse. In this case the change amount threshold value is 0.2 nA/mm² whenthe response voltage E2 is applied, and 0.5 nA/mm² when the non-responsevoltage E1 is applied, however the change amount threshold values areappropriately set according to such factors as the specification of thesensor section 4 and the sampling periods.

Explanation follows regarding a testing mode processing routine executedduring the testing mode of the continuous glucose monitoring device 1 ofthe third exemplary embodiment, with reference to FIG. 17.

At step 300 determination is made as to whether or not it is a timingfor executing the processing of the testing mode. Processing transitionsto step 302 when determined that the execution timing for the testingmode has arrived. However when determined that the execution timing forthe testing mode has not yet arrived determination at step 300 isrepeated until determined that the execution timing has arrived.

In step 302 the non-response voltage E1 is applied for a specific periodof time. For example a voltage of −200 mV is applied for 240 seconds.Then, in step 304, at a specific sampling interval (for example 5seconds), the amount of change of the response current ΔI_(E1) ismeasured. Then at step 306, with the timing when the non-responsevoltage E1 is applied at step 302 as a starting point, the time T_(E1)until the measured amount of change of the response current ΔI_(E1)becomes smaller than a specific change amount threshold value ΔIth_(E1)is computed. Note that explanation is made of a case in which the amountof change of the response current ΔI_(E1) is an absolute value. However,it is not limited to an absolute value, and the actual value may beemployed. In such a case, the time T_(E1) until the amount of change ofthe response current ΔI_(E1) becomes larger than a specific changeamount threshold value ΔIth_(E1) is computed. In other words, the timeT_(E1) until the amount of change of the response current ΔI_(E1)reaches a value within a specific range can be computed. The sameapplies to the amount of change of the response current ΔI_(E2)mentioned below.

Then at step 308 the response voltage E2 is applied for a specificperiod of time. For example +400 mV is applied for 120 seconds. Then atstep 310, at a specific sampling interval (for example every 5 seconds)the amount of change of the response current ΔI_(E2) is measured. Thenat step 312, with the timing when the response voltage E2 is applied atstep 308 as a starting point, the time T_(E2) until the amount of changeof the response current ΔI_(E2) becomes smaller than a specific changeamount threshold value ΔIth_(E2) is computed.

Then at step 314 comparison is made of the time T_(E1) computed at step306 and a time threshold value Tth_(E1), and of the time T_(E2) computedat step 312 and a time threshold value Tth_(E2). Determination is thenmade as to whether or not both the time T_(E1) is smaller than the timethreshold value Tth_(E1) and the time T_(E2) is smaller than the timethreshold value Tth_(E2). The time threshold value Tth_(E1) is set withreference to the time when the non-response voltage E1 is applied untilthe amount of change of the response current ΔI_(E1) becomes smallerthan the change amount threshold value ΔIth_(E1) for a case when asensor with normal semi-permeable membrane 45 is employed. Similarly,the time threshold value Tth_(E2) is set with reference to the time whenthe non-response voltage E2 is applied until the amount of change of theresponse current ΔI_(E2) becomes smaller than the change amountthreshold value ΔIth_(E2) for a case when a sensor with a normalsemi-permeable membrane 45 is employed. For example, as shown in FIG.16A, when the response voltage E2 applied with CA4% Spin as a normalsensor, the time threshold value Tth_(E2) can be set at 70±α seconds.Similarly, as shown in FIG. 16B, when the non-response voltage E1 isapplied with CA4% Spin as a normal sensor, the time threshold valueTth_(E1) can be set at 58±α seconds. Here, α can be set between 5 to 20seconds, for example. When both time T_(E1)<time threshold valueTth_(E1) and time T_(E2)<time threshold value Tth_(E2), determination ismade that the state of the semi-permeable membrane 45 has changed,namely that a defect has occurred, and processing transitions to step320. However, processing transitions to step 316 when either timeT_(E1)≧time threshold value Tth_(E1) and/or time T_(E2)≧time thresholdvalue Tth_(E2).

At step 316 determination is made as to whether or not the time T_(E1)is smaller than the time threshold value Tth_(E1) but the time T_(E2) isequal to the time threshold value Tth_(E2) or greater, or the timeT_(E1) is equal to the time threshold value Tth_(E1) or greater but thetime T_(E2) is smaller than the time threshold value Tth_(E2). Namelydetermination is made as to whether or not one or other of the times Tis smaller than the respective time threshold values Tth. When negativedetermination is made, since both the times T are equal to therespective time threshold values Tth or greater, determination is madethat the state of the semi-permeable membrane 45 has not changed, namelythat it is normal, and processing is ended. However, when determinedthat only one of the times T is smaller than the time threshold valueTth processing transitions to step 318 where determination is made as towhether or not the processing of step 314 or step 316 is already are-test. When the current processing is processing for the first time,processing returns to step 302 and the processing is repeated and are-test performed. However, when the processing is already beingperformed as a re-test, the state of the sensor is determined to benormal and processing ended.

In step 320, a defect ratio of the semi-permeable membrane 45 is derivedbased on the time T_(E2) computed at step 312, correction values for theresponse currents measured in the monitoring mode are computed accordingto the defect ratio, and stored in the storage section 35.

More specifically, first the relationship between the time T_(E2) andthe defect ratio is plotted, as shown in FIG. 18A. For instance, foreach of the sensors shown in FIG. 6, the times T_(E2) in the case thechange amount threshold value ΔIth is set at 0.2 nA/mm² are computed,and the relationship between the times T_(E2) and the defect ratios foreach of the sensors are plotted on a graph with the horizontal axis asrepresenting time T_(E2) and the vertical axis as representing defectratio. Note that FIG. 18A is the same as FIG. 10. A correspondencebetween the plotted time T_(E2) and the defect ratio is derived andpre-stored in the storage section 35. The correspondence of the timeT_(E2) to the defect ratio is then employed to derive the defect ratiocorresponding to a time T_(E2) computed at step 312. For example, in theexample of FIG. 18A, if the time T_(E2) is 60 seconds then the defectratio is derived as 31.5%. As shown in FIG. 18B, when determining thecorrespondence of the time T_(E1) and the defect ratio, the defect ratiomay be derived employing the time T_(E1) computed at step 306.Alternatively configuration may be made such that both the defect ratiobased on the time T_(E1) and the defect ratio based on the time T_(E2)are derived, and the average value, the larger value, or the smallervalue of these defect ratios is then employed as the defect ratio. Then,as in the first exemplary embodiment, the derived relationship betweenthe defect ratio and the sensitivity normal-error difference is employedto derive the sensitivity normal-error difference corresponding to thederived defect ratio.

As explained above, according to the continuous glucose monitoringdevice of the third exemplary embodiment, the times employed to test thestate of the semi-permeable membrane 45 are both the time until theamount of change of the response current immediately after a voltagethat obtains a response caused by glucose is applied becomes less than apredetermined threshold value, and the time until the amount of changeof the response current immediately after a voltage that does not obtaina response caused by glucose is applied becomes less than apredetermined threshold value. Hence sensor state testing can beperformed in a short time, stably and with good precision withoutproviding plural sets of working electrodes and counter electrodes. Inparticular, since the change in response current immediately aftervoltage application is employed for testing, the execution time for thetesting mode can be made shorter than in cases employing the time untilthe response current reaches a steady state. This is more efficient incases such as the present exemplary embodiment in which continuousmonitoring is performed.

In the third exemplary embodiment, explanation is given of a case inwhich a defect in a sensor is determined to occur when it has beendetermined that both the time T_(E1) until the amount of change of theresponse current immediately after application of the non-responsevoltage E1 becomes smaller than a predetermined amount of change and thetime T_(E2) until the amount of change of the response currentimmediately after application of the response voltage E2 becomes smallerthan a predetermined amount of change are less than specific respectivethreshold values (Tth_(E1) and Tth_(E2)). However, configuration may bemade such that a defect in a sensor is determined to occur when timeT_(E1)<Tth_(E1) alone. Since the response current to non-responsevoltage E1 is a background response current caused by the peculiaritiesof the sensor including the external layer membrane and excludes aresponse current caused by glucose, the determination precision can beraised by determining whether or not a defect is present in a sensorusing the change in response current to the non-response voltage E1.Furthermore, in cases in which at least the amount of change to theresponse current to the non-response voltage E1 is employed togetherwith additionally employing the amount of change in the response currentto the response voltage E2, determination is then made employing changesin response current to two different voltages, and determinationprecision can be further raised.

Explanation has been given of a case in which the response voltage E2 isapplied (steps 308 to 312) after applying the non-response voltage E1 inthe third exemplary embodiment (steps 302 to 306). However configurationmay be made such that first the processing of steps 308 to 312 areexecuted for applying the response voltage E2, and then the processingof steps 302 to 306 are executed for applying the non-response voltageE1.

In the third exemplary embodiment explanation has been given of cases inwhich the amount of change per specific period of time of the responsecurrent immediately after application of each of the voltages is used asthe change of the response current, and the times until the amount ofchange becomes less than predetermined amounts of change are employed.There is, however, no limitation thereto and configuration may be madesuch that the rate of change or the pattern of change of responsecurrent immediately after application of each of the voltages isemployed for the change of the response current.

Moreover, as in the second exemplary embodiment, the amount of change inthe response current a predetermined period after application of theresponse voltage and the non-response voltage can also be employed. Insuch a case, the amount of change in the response current apredetermined period (here, 40 seconds) after application of thenon-response voltage E1 (−200 mV) using each of the sensors shown inFIG. 6 is illustrated in FIG. 19. Note that the amount of change in theresponse current when the non-response voltage E1 is applied is the sameas in FIG. 12. As seen from FIG. 19, the change in response current issmaller for thinner membrane thickness sensors CA3% Spin and CA2% Spinthan for the thickest sensor CA4% Spin. The cause of this difference intime is postulated to be due to the difference in charge amount of theelectric double layer on the electrode arising from the difference instates of the CA membrane. Moreover, the change of the response currentis smaller in the sensors with simulated defective membranes CA4% Spin-Ato -D than in the CA4% Spin sensor with completely covered surface.Using such a result, as in the second exemplary embodiment, acorrespondence of the amount of change of the response current AI to thedefect ratio can be determined as shown in FIG. 14 and FIG. 20.

Furthermore, in the third exemplary embodiment explanation has beengiven of cases of voltage patterns in which the non-response voltage E1and the response voltage E2 are applied alternately, as shown in FIG. 5,however the voltage pattern does not need to always be a pattern inwhich the non-response voltage E1 and the response voltage E2 areapplied alternately. For example, as shown in FIG. 21 (1) to (4),configuration may be made such that voltage application is in steps withcombinations of plural constant voltages of different electricalpotentials. Configuration may be made such that at a first step (a firststep of a combination of a state in which the non-response voltage E1 isapplied for a fixed period of time, and a state in which the responsevoltage E2 is applied for a fixed period of time) includes threeconstant voltages, as shown in FIGS. 21 (1) to (4), however the numberof constant voltages may be set at 2 or 4 or more. The testing frequencyof the external layer membrane can accordingly be raised by the increasein the number of points at which electrical potential is changed.

Furthermore, in each of the above exemplary embodiments, explanation hasbeen given of cases in which the analyzing device of the presentinvention is applied to a continuous glucose monitoring device, howevermonitoring target composition to be tested is not limited to glucose.Furthermore, application is not limited a CGM device and application canalso be made to a Self-Monitoring of Blood Glucose (SMBG) device. Insuch cases configuration may be made such that testing is executed bythe testing mode being selected by a user and a sample liquid beingdripped on the sensor section by a user.

In each of the above exemplary embodiments explanation has been given ofcases in which a correction value is computed when a defect in a sensor(semi-permeable membrane) is detected, however configuration may be madesuch that a signal indicating that a defect in a sensor has occurred isoutput when a defect in a sensor is detected, and a correction value iseither computed for output with this signal or not even computed. Insuch cases configuration may be made such that an output unit and analarm unit are provided to the analyzing device, and when a defect in asensor is detected a signal indicating that a defect in a sensor hasoccurred is output from the output unit to the alarm unit. Morespecifically, a display, speaker or vibration unit may be provided asthe alarm unit, such that a message that a defect in a sensor hasoccurred is displayed on the display, sound is output from the speaker,or the device is caused to vibrate when the alarm unit receives thesignal from the output unit. Configuration may also be made such thatthe signal from an output unit is output for example to an external dataprocessing apparatus and warning that a defect in a sensor has occurredis made by an alarm unit provided to the external data processingapparatus. Note that the configuration of the alarm unit is not limitedto the examples referred to above.

In each of the above exemplary embodiments, explanation has been givenof cases in which the response voltage or the non-response voltage isapplied for specific periods of time. However configuration may be madesuch that that application of the response voltage or the non-responsevoltage is halted at the point in time when it is determined the amountof change of the response current is smaller than the change amountthreshold value, and then the subsequent processing is executed.

In each of the above exemplary embodiments, explanation has been givenof cases in which the end portion of the sensor section (the electrodeportion) is configured as the example shown in FIG. 3, however otherconfigurations can be employed. For example, configuration may be madesuch that the semi-permeable membrane 45 is formed so as to cover aworking electrode portion 42A and a counter electrode portion 42B asshown in FIG. 22(1), or a semi-permeable membrane 45 may be formedlayered on a reagent layer 44 as shown in FIG. 22(2). Note that anenzyme portion 43 is disposed in a reagent layer above the workingelectrode portion 42A, although the enzyme portion 43 has been omittedfrom illustration in FIG. 22.

There are no particular limitations to the storage medium for storing aprogram of the present invention, and configuration may be made forexample with a hard disk or with a ROM. Configuration may also be madewith a CD-ROM, DVD disk, magneto-optical disk or IC card. Configurationmay also be made such that the program is downloaded from a device suchas a server connected to a network.

1.-12. (canceled)
 13. A sensor testing method comprising: applying to areagent layer of a sensor section at least one of a first voltage acrossa first electrode and a second electrode to generate a response currentby reaction of a reagent present in the reagent layer with a targetsubstance in a sample liquid and a second voltage that results in noresponse current or substantially no response current, where the sensorsection comprises the reagent layer, an electrode section comprising thefirst electrode, the second electrode and an external layer membrane formaking contact with the reagent layer; measuring the response currentflowing between the first electrode and the second electrode; andcomputing a time required for an amount of change in the responsecurrent per specific amount of change in time resulting from theapplication of the first voltage to reach a value in a predeterminedfirst specific range prior to when the response current reaches a steadystate for determining whether there is a defect present in the externallayer membrane, or computing a time required for an amount of change inthe response current per specific amount of change in time resultingfrom the application of the second voltage to reach a value in apredetermined second specific range prior to when the response currentreaches a steady state for determining whether there is a defect presentin the external layer membrane.
 14. (canceled)
 15. The sensor testingmethod of claim 13, further comprising: storing a first relationshipbetween the time required for an amount of change in the responsecurrent per specific amount of change in time resulting from theapplication of the first voltage to reach a value in a predeterminedfirst specific range and a set of defect ratios corresponding to thetime required for the response current resulting from the application ofthe first voltage; storing a second relationship between the timerequired for an amount of change in the response current per specificamount of change in time resulting from the application of the secondvoltage to reach a value in a predetermined second specific range and aset of defect ratios corresponding to the time required for the responsecurrent resulting from the application of the second voltage; andcorrecting the response current value measured when a defect isdetermined to have occurred in the external layer membrane, wherein thecorrecting is based on at least one of the first relationship or thesecond relationship.
 16. The sensor testing method of claim 15, whereinthe correcting of the response current value measured is based on arelationship between the defect ratio of the external layer membrane andthe response current value measured from the sensor section providedwith an external layer membrane having defects corresponding to thedefect ratio.
 17. The sensor testing method of claim 16, wherein thedefect ratio based on both the first relationship and the secondrelationship is computed as the average value, the maximum value or theminimum value of a first defect ratio estimated based on the firstrelationship and a second defect ratio estimated based on the secondrelationship.
 18. The sensor testing method of claim 13, furthercomprising outputting a signal indicating that a defect has occurred inthe sensor section when a defect is determined to have occurred in theexternal layer membrane.
 19. The sensor testing method of claim 13,wherein the first voltage and the second voltage are appliedalternately.
 20. The sensor testing method of claim 13, wherein theresponse current flowing between the first electrode and the secondelectrode is continuously measured.
 21. The sensor testing method ofclaim 13, wherein the sensor section is disposed under the skin of auser of the method and the target substance is present under the skin.22. The sensor testing method of claim 13, wherein the reagent layerextracts electrons from the target substance and supplies the extractedelectrons to the electrode section.
 23. The sensor testing method ofclaim 13, wherein the reagent in the reagent layer includes an enzyme.